Chemical identification

Zearalenone is a natural estrogen, a mycotoxin from resorcylic acid lactone group. Zearalenone is a non-steroidal estrogenic mycotoxin produced by
several Fusarium spp. It has been implicated in numerous
mycotoxicoses in farm animals, especially in pigs. Zearalenone is
heat-stable and is found worldwide in a number of cereal crops, such
as maize, barley, oats, wheat, rice, and sorghum (Kuiper-Goodman et
al., 1987; Tanaka et al., 1988a) and also in bread (Aziz et al.,
1997). Zearalenone was shown to be produced on corn by Fusarium
isolates from Australia, Europe, and North America (Vesonder et al.,
1991) and in New Zealand (diMenna et al., 1997), the Philippines,
Thailand, and Indonesia (Yamashita et al., 1995). The occurrence of
zearalenone in food and feed was also demonstrated in South America
(Dalcero et al., 1997; Molto et al., 1997), Africa (Doko et al.,
1996), China and the former USSR (Ueno et al., 1986). Fusarium
isolates from bananas can also produce zearalenone

Molecular weight:

318.40

InChl Key:

MBMQEIFVQACCCH-QBODLPLBSA-N

Canonical SMILES:

CC1CCCC(=O)CCCC=CC2=CC(=CC(=C2C(=O)O1)O)O

Isomeric SMILES:

C[C@H]1CCCC(=O)CCC/C=C/C2=CC(=CC(=C2C(=O)O1)O)O

Further Information

Solubility ( literature ):

Zearalenone is slightly soluble in hexane and progressively more in benzene, acetonitrile, dichloromethane, methanol, acetone. In water: 20 mg/L .

Compound Classification:

Mycotoxin

A resorcylic acid lactone

Sexual reproduction in Fusarium is regulated by the fungal sex hormone zearalenone, which is known to be synthesized only by species of Gibberella zeae (Fusarium roseum)

Storage, handling:

Store in a freezer upon arrival, at -10°C to -25°C

Keep the lid tightly closed.

Avoid exposing to strong direct light.

Other vendors may recommend higher temperatures for storage.

Applications:

The resorcylic acid lactones have estrogenic activity. Zearalenone and its derivates were used as veterinary anabolic or estrogen substitutes.

Determination of zearalenone and its metabolites in urine, plasma and faeces of horses by HPLC-APCI-MS.

The paper describes a method for the sensitive and selective determination of zearalenone and its metabolites in urine, plasma and faeces of horses by high performance liquid chromatography and atmospheric pressure chemical ionisation (APCI) mass spectrometry (MS). While only one step sample clean-up by an immunoaffinity column (IAC) was sufficient for plasma samples, urine and faeces samples had to be prepared by a combination of a solid-phase extraction (SPE) and an immunoaffinity column. The method allows the simultaneous determination of zearalenone and all of its metabolites; alpha-zearalenol, beta-zearalenol, alpha-zearalanol, beta-zearalanol and zearalanone. Dideuterated zearalanone was used as internal standard for quantification and the study of the matrix effect. Recovery rates between 56 and slightly above 100% were achieved in urine samples, and more than 80% in plasma and faeces samples. The limits of detection ranged from 0.1-0.5 microg/l or microg/kg, the limits of quantification from 0.5-1.0 microg/l or microg/kg. The practical use of the method is demonstrated by the analysis of spiked and naturally contaminated urine, plasma and faeces of horses.

PMID: 16828347

Toxicol Sci. 2006 Jun;91(2):448-55. Epub 2006 Mar 17

The mycoestrogen zearalenone induces CYP3A through activation of the pregnane X receptor.

Ding X, Lichti K, Staudinger JL.

Department of Pharmacology and Toxicology, University of Kansas, Lawrence, Kansas 66045, USA.

Zearalenone is a mycoestrogen that is produced in the fungi Fusarium graminearum, Fusarium culmorum, Fusarium equiseti, and Fusarium crookwellense. These fungi commonly exist in agricultural products. Human pregnane X receptor (hPXR) is a ligand-activated transcription factor that regulates the expression of numerous hepatic drug-metabolizing enzymes, including several clinically important cytochrome P450s. In this report, we show that zearalenone is an efficacious ligand for hPXR. We also describe the creation and validation of a novel adenoviral-mediated transduction protocol used to express functional FLAG-tagged-hPXR protein in a transformed cell line (HepG2) and primary cell types (cultured hepatocytes). Treatment of hPXR-transduced HepG2 cells with zearalenone induces expression of CYP3A4, the "prototypical" PXR-target gene in human liver. Treatment of hPXR-transduced cultured hepatocytes isolated from PXR-knockout mice with zearalenone induces the expression of Cyp3a11, the prototypical murine hepatic PXR-target gene. Using mammalian two-hybrid assays, we show that zearalenone displaces the nuclear receptor corepressor protein N-CoR from hPXR, while it recruits coactivator proteins steroid receptor coactivator-1, Glucocorticoid Receptor-Interacting Protein 1 and PPAR-Binding protein (GRIP1) and PBP to hPXR. Concentration-response analysis using a PXR-responsive reporter gene assay reveals that zearalenone activates hPXR with an EC50 value of approximately 1.5 microM. Because activation of hPXR represents the molecular basis of an important class of drug interactions, our findings suggest that studies to investigate the potential of zearalenone to induce the metabolism of other drugs in humans are warranted. In addition, due to the limited availability of primary human hepatocytes, our adenoviral-mediated hPXR expression protocol will likely prove useful in studies of the xenobiotic response.